The burden of heat-related mortality attributable to recent human-induced climate change.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

Study of the Effect of Hyperbaric Oxygen Therapy on the Viability of Dorsal Cutaneous Flaps in Tobacco-Exposed Rats.

BACKGROUND: Smoking causes a threefold increase in the risk of surgical complications in flaps. Hyperbaric oxygen therapy (HBOT) increases the viability of chronic wounds. However, there are few studies concerning the effects of HBOT on surgical flaps in patients who smoke. This study aimed to analyze the effect of HBOT on the viability of cutaneous flaps in tobacco-exposed rats. METHODS: Twenty Wistar rats were exposed to tobacco smoke for two months. Following this period, all animals underwent a dorsal cutaneous flap (3 × 10 cm) surgery and were divided into two groups: control (n = 10) and HBOT (n = 10). HBOT was performed in seven daily sessions (2 ATA, 90 min). After seven days, the animals were euthanized. The outcomes were total area, viable area, viable area/total area rate, analysis of dermal appendages and angiogenesis (hematoxylin-eosin), and gene expression analysis of iNOS and VEGF-a biomarkers. RESULTS: The HBOT group showed an increase in viable area compared with the control group (84% versus 47%, p = 0.009, respectively). The HBOT group also showed an increase in appendage units (1.69 ± 0.54 versus 1.87 ± 0.58, p = 0.04) and angiogenesis density (1.29 ± 0.45 versus 1.82 ± 0.64, p < 0.001) compared to the control group. There was a difference between the control and HBOT groups in iNOS levels (0.926 ± 1.4 versus 0.04 ± 0.1 p = 0.002, respectively). However, this study did not show a difference between the groups concerning the gene expression of VEGF-a. CONCLUSION: The use of hyperbaric oxygen therapy increased the viability of cutaneous flaps in tobacco-exposed rats and decreased iNOS mRNA levels; however, it did not change VEGF-a levels. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The role of air pollution in myocardial remodeling.

BACKGROUND: Excessive air pollution in urban environments can impact morbidity and mortality. The authors evaluated the role of particulate matter2.5 (PM2.5) in structural, geometric, and functional remodeling in hearts, using an experimental model of myocardial infarction. METHODS AND FINDINGS: Seventy-five rats were divided into 5 groups: control (CG), CG exposed to PM2.5 pollution (CGP), myocardial infarcted group (MI), infarcted group immediately exposed to pollution (IGP-I), and infarcted group previously exposed to pollution and kept exposed after infarction (IGP-II). Greater deposition of interstitial collagen occurred in the left ventricle in CGP, MI, IGP-I, and IGP-II groups compared with that in controls (p = 0.002 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). In the right ventricle, greater collagen deposition existed in CGP, MI, IGP-I, and IGP-II compared with that in CG (p<0.021 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). At the end of the study, CG had a higher mean shortening fraction than the other groups had (p≤0.03). Left ventricular systolic diameter was lower in CG than in infarcted groups (p≤0.003). The infarcted groups had greater expression of TGF-ß (p≤0.04). PM2.5 increased the expression of TGF-ß in the IGP-II compared with the MI group (p = 0.004). The TNF-α gene was overexpressed in the IGP-II compared with the CGP group (p = 0.012). INF-γ gene expression was greater in IGP-II (p≤0.01). Oxidative stress analysis showed a higher glutathione concentration in CGP (p = 0.03), MI (p = 0.014), and IGP-I (p = 0.008) compared with that in CG. CONCLUSIONS: PM2.5 stimulates the deposition of fibrosis in the myocardium of healthy hearts, but not in infarcted hearts. PM2.5 modulates the inflammatory response, which was greater in the IGP-II group. It also modulates oxidative stress in healthy hearts but not in infarcted hearts.

Changes over time in the prevalence of asthma, rhinitis and atopic eczema in adolescents from Taubaté, São Paulo, Brazil (2005-2012): Relationship with living near a heavily travelled highway.

BACKGROUND: The prevalence of allergic diseases is increasing. We evaluated temporal trends in the prevalence of asthma, rhinitis and eczema in adolescents (13-14 years) living in Taubaté, SP, Brazil (2005-2012) and assessed the relationship between these prevalences and the residential proximity to Presidente Dutra Highway (PDH, a heavily travelled highway). METHODS: This cross-sectional study of adolescents (N=1039) from public and private schools was evaluated using the standard questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) plus a question about their place of residence in relation to PDH. The data obtained were compared to the 2005 data using a chi-square test or Fisher's exact test. An analysis by groups consisting of two phases (two-step cluster) was used to evaluate the effect of living near PDH. RESULTS: There was a lifetime increase in the prevalence of active asthma (15.3% vs. 20.4%, p=0.005) and physician-diagnosed asthma (6.8% vs. 9.2%, p=0.06) and a decrease in the symptoms of active rhinitis (36.6% vs. 18.5%) between 2005 and 2012. A high frequency of asthma and rhinitis (18.1% vs. 23.2%, respectively) was observed among adolescents living close or very close to PDH; furthermore, 85.6% of the adolescents without symptoms of asthma or rhinitis lived far from PDH. CONCLUSION: An increase in the prevalence of asthma and a decrease in the prevalence of rhinitis were observed during the studied period. Living near PDH was associated with higher rates of asthma, rhinitis, and eczema.

The effects of urban particulate matter on the nasal epithelium by gender: An experimental study in mice.

Nose is the first portion of the respiratory system into contact with air pollution particles, including organic compounds that could act as endocrine releasers. The objective was to identify and quantify estrogenic receptor-ß (ERß), aryl hydrocarbon receptor (AhR), the cytochrome P450 enzymes CYP1A1, 1A2, 1B1, and mucus profile in the nasal epithelium of mice. BALB/c mice male (n = 32) and female (n = 82) in proestrus, estrus and diestrus were divided into two groups: 1) exposed to ambient air; 2) concentrated ambient particles (CAPs) to achieve an accumulated dose (concentration vs. time product) of 600 µg/m(3), the time of the exposure was controlled to ensure the same concentration for all groups (5 days per week for 40-51 days). RT-PCR (Erß-1, Erß-2, Ahr, Cyp1a1, Cyp1a2, Cyp1b1), immunohistochemistry and morphometry (ERß, AhR) were used to analyze. The mucus profiles were examined using acid (Alcian Blue) and neutral (periodic acid Schiff's) stains. Exposed females had significantly lower levels of Erß-2 mRNA than exposed males (p = 0.036). Cyp1b1 mRNA in diestrus females was significantly lower in the CAP-exposed group compared with the ambient air group (p ≤ 0.05). ERß expression in the epithelium and submucosa nucleus was lower in estrus exposed to CAPs compared with ambient air. CAPs increases AhR in the epithelium (p = 0.044) and submucosa (p = 0.001) nucleus of female when compared with male mice. Exposure to CAPs, also led to relatively increased acidic content in the mucus of males (p = 0.048), but decreased acidic content in that of females (p = 0.04). This study revealed sex-dependent responses to air pollution in the nasal epithelium that may partially explain the predisposition of females to airway respiratory diseases.

Air particulate matter exacerbates lung response on Sjögren's Syndrome animals.

Epidemiological studies have associated air particulate matter (PM) inhalation with a decline in lung function and increased morbo-mortality due to cardiorespiratory diseases, particularly in susceptible populations. Sjögren's Syndrome (SS) is a chronic autoimmune disease characterized by cellular infiltration in exocrine glands and extraglandular tissue, being the respiratory tract an important target. We evaluated the effect of PM on the airways of NOD mice, which develop SS and BALB/c mice. BALB/c or NOD mice (2-3 months) were randomized in two groups and exposed to intranasal instillation either with saline (control) or ROFA solution (1mg/kg body weight). After 24h, mice were euthanized in order to perform lung histology, or measure total cell number (TCN), differential cell count (DCC) and superoxide anion generation in the bronchoalveolar lavage (BAL) fluid. BALB/c mice showed normal histoarchitecture, while NOD mice showed lymphocytic peribronchial infiltrates. ROFA exposure affected the respiratory tract from both BALB/c and NOD mice, with a significant increase in the TCN (p<0.05) and generation of O2(-) (p<0.05), as well as an imbalance in the DCC (p<0.05). All histological observations correlated with the cellular parameters evaluated. Lesions in NOD mice were more severe than those of BALB/c, showing cellular infiltration in the alveoli and leading to a greater decrease in the alveolar space. We have proved that in this experimental Sjögren's Syndrome animal model (NOD mice); airborne pollution exacerbates pre-existing pulmonary lesions. These findings show experimental evidence on the harmful effects of airborne pollution on the airways of patients with Sjögren's Syndrome.

Direct and indirect air particle cytotoxicity in human alveolar epithelial cells.

Air particulate matter has been associated with adverse impact on the respiratory system leading to cytotoxic and proinflammatory effects. The biological mechanisms behind these associations may be initiated by inhaled small size particles, particle components (soluble fraction) and/or mediators released by particle-exposed cells (conditioned media). The effect of Urban Air Particles from Buenos Aires (UAP-BA) and Residual Oil Fly Ash (ROFA) a surrogate of ambient air pollution, their Soluble Fractions (SF) and Conditioned Media (CM) on A549 lung epithelial cells was examined. After 24 h exposure to TP (10 and 100 µg/ml), SF or CM, several biological parameters were assayed on cultured A549 cells. We tested cell viability by MTT, superoxide anion (O2(-)) generation by NBT and proinflammatory cytokine (TNFα, IL-6 and IL-8) production by ELISA. UAP-BA particles or its SF (direct effect) did not modify cell viability and generation of O2(-) for any of the doses tested. On the contrary, UAP-BA CM (indirect effect) reduced cell viability and increased both generation of O2(-) and IL-8 production. Exposure to ROFA particles, SF or ROFA CM reduced proliferation and O2(-) but, stimulated IL-8. It is worth to note that UAP-BA and ROFA depicted distinct effects on particle-exposed A549 cells implicating morphochemical dependence. These in vitro findings support the hypothesis that particle-induced lung inflammation and disease may involve lung-derived mediators.

Repeated inhalation of crack-cocaine affects spermatogenesis in young and adult mice.

To investigate the effects of repeated crack-cocaine inhalation on spermatogenesis of pubertal and mature Balb/c mice, ten young (Y(ex)) and ten adult (A(ex)) Balb/c mice were exposed to the smoke from 5 g of crack with 57.7% of pure cocaine in an inhalation chamber, 5 days/week for 2 months. The young (Y(c)) and adult (A(c)) control animals (n = 10) were kept in a specially built and controlled animal house facility. The morphologic analysis of both testes of all animals included the analysis of quantitative and qualitative histologic parameters to assess the effect of crack-cocaine on spermatogenesis and Leydig cells. Apoptosis was determined by immunolabeling with caspase-3 antibodies. Compared to the Y(c) animals, Y(ex) animals showed a significant reduction in the number of stage VII tubules per testis (p = 0.02), Sertoli cells (p < 0.001) and elongated spermatids (p = 0.001). Comparisons between the Y(ex) and A(ex) groups identified a significant reduction in the number of Sertoli cells (p < 0.001) and round spermatids (p < 0.001) in the Y(ex) group and a significant increase in apoptotic Leydig cells (p = 0.04) in the A(ex) group. The experimental results indicate that crack-cocaine smoke inhalation induced spermatogenesis disruption in chronically exposed mice, particularly in pubertal mice.

Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1.

Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice.

Air pollution is associated with morbidity and mortality induced by respiratory diseases. However, the mechanisms therein involved are not yet fully clarified. Thus, we tested the hypothesis that a single acute exposure to low doses of fine particulate matter (PM2.5) may induce functional and histological lung changes and unchain inflammatory and oxidative stress processes. PM2.5 was collected from the urban area of São Paulo city during 24 h and underwent analysis for elements and polycyclic aromatic hydrocarbon contents. Forty-six male BALB/c mice received intranasal instillation of 30 µL of saline (CTRL) or PM2.5 at 5 or 15 µg in 30 µL of saline (P5 and P15, respectively). Twenty-four hours later, lung mechanics were determined. Lungs were then prepared for histological and biochemical analysis. P15 group showed significantly increased lung impedance and alveolar collapse, as well as lung tissue inflammation, oxidative stress and damage. P5 presented values between CTRL and P15: higher mechanical impedance and inflammation than CTRL, but lower inflammation and oxidative stress than P15. In conclusion, acute exposure to low doses of fine PM induced lung inflammation, oxidative stress and worsened lung impedance and histology in a dose-dependent pattern in mice.

Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling.

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-ß1 (TGF-ß1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-ß1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-ß1.

Severe novel influenza A (H1N1) infection in cancer patients.

BACKGROUND: The natural history and consequences of severe H1N1 influenza infection among cancer patients are not yet fully characterized. We describe eight cases of H1N1 infection in cancer patients admitted to the intensive care unit of a referral cancer center. PATIENTS AND METHODS: Clinical data from all patients admitted with acute respiratory failure due to novel viral H1N1 infection were reviewed. Lung tissue was submitted for viral and bacteriological analyses by real-time RT-PCR, and autopsy was conducted on all patients who died. RESULTS: Eight patients were admitted, with ages ranging from 55 to 65 years old. There were five patients with solid organ tumors (62.5%) and three with hematological malignancies (37.5%). Five patients required mechanical ventilation and all died. Four patients had bacterial bronchopneumonia. All deaths occurred due to multiple organ failure. A milder form of lung disease was present in the three cases who survived. Lung tissue analysis was performed in all patients and showed diffuse alveolar damage in most patients. Other lung findings were necrotizing bronchiolitis or extensive hemorrhage. CONCLUSIONS: H1N1 viral infection in patients with cancer can cause severe illness, resulting in acute respiratory distress syndrome and death. More data are needed to identify predictors of unfavorable evolution in these patients.

Subchronic effects of nasally instilled diesel exhaust particulates on the nasal and airway epithelia in mice.

Diesel exhaust is the major source of ultrafine particles released during traffic-related pollution. Subjects with chronic respiratory diseases are at greater risk for exacerbations during exposure to air pollution. This study evaluated the effects of subchronic exposure to a low-dose of diesel exhaust particles (DEP). Sixty male BALB/c mice were divided into two groups: (a) Saline: nasal instillation of saline (n = 30); and (b) DEP: nasal instillation of 30 microg of DEP/10 microl of saline (n = 30). Nasal instillations were performed 5 days a week, over 30 and 60 days. Animals were anesthetized with pentobarbital sodium (50 mg/kg intraperitoneal [i.p.]) and sacrificed by exsanguination. Bronchoalveolar lavage (BAL) fluid was performed to evaluate the inflammatory cell count and the concentrations of the interleukin (IL)-4, IL-10, and IL-13 by enzyme-linked immunosorbent assay (ELISA). The gene expression of oligomeric mucus/gel-forming (Muc5ac) was evaluated by real-time polymerase chain reaction (PCR). Histological analysis in the nasal septum and bronchioles was used to evaluate the bronchial and nasal epithelium thickness as well as the acidic and neutral nasal mucus content. The saline group (30 and 60 days) did not show any changes in any of the parameters. However, the instillation of DEP over 60 days increased the expression of Muc5ac in the lungs and the acid mucus content in the nose compared with the 30-day treatment, and it increased the total leukocytes in the BAL and the nasal epithelium thickness compared with saline for 60 days. Cytokines concentrations in the BAL were detectable, with no differences among the groups. Our data suggest that a low-dose of DEP over 60 days induces respiratory tract inflammation.

Structural alterations in adult rat carotid bodies exposed to hyperbaric oxygenation.

UNLABELLED: Inhibition of carotid body (CB) function is the main mechanism involved in the attenuation of respiratory drive observed during hyperoxia. However, only a few studies at 5.0 atmospheres absolutes (ATA) have analyzed carotid body structure or function in hyperbaric oxygenation (HBO2) situations. We hypothesized that rats will present CB structural alterations when exposed to different lower hyperbaric oxygen doses enough to alter their chemosensory response to hypoxia. METHODS: Twenty-one adult male Wistar rats, divided into three groups, were maintained in room air or exposed to O2 at 2.4 or 3.0 ATA for six hours. Histological, ultrastructural and immunohistochemical analyses for neuronal nitric oxide synthase (nNOS) and F2-isoprostane were performed in the excised CBs. RESULTS: Histological analyses revealed signs of intracellular edema in animals exposed to both conditions, but this was more marked in the 3.0 ATA group, which showed ultrastructural alterations at the mitochondrial level. There was a significant increase in the volume density of intraglomic-congested capillaries in the 3.0 ATA group associated with an arteriolar vasoconstriction. In the 2.4 ATA group, there was a relative increase of glomic light cells and a decrease of glomic progenitor cells. Additionally, there was a stronger immunoreactivity for F2-isoprostane in the 3.0 ATA O2-exposed carotid bodies. The glomic cells stained positive for nNOS, but no difference was observed between the groups. Our results show that high O2 exposures may induce structural alterations in glomic cells with signs of lipid peroxidation. We further suggest that deviation of blood flow toward intraglomic capillaries occurs in hyperbaric hyperoxia.

Evaluation of DNA damage by the alkaline comet assay of the olfactory and respiratory epithelia of dogs from the city of São Paulo, Brazil.

Animals kept as pets may be considered sentinels for environmental factors to which humans could be exposed. Olfactory and respiratory epithelia are directly subjected to airborne factors, which could cause DNA lesions, and the alkaline comet assay is considered a reliable tool for the assessment of DNA damage. The objective of this work is to evaluate the extent of DNA damage by the comet assay of the olfactory and respiratory epithelia of dogs from different regions of the city of São Paulo, Brazil. Thirty-three clinically healthy dogs, aged 5 years or more, were used in the study, with 7 from the North region of São Paulo, 7 from the South region, 3 dogs from the East region, and 16 dogs from the West city region. Three dogs younger than 6 months were used as controls. DNA damage was analyzed by the alkaline comet assay. We observed no difference in histopathological analysis of olfactory and respiratory epithelia between dogs from different regions of São Paulo. Dogs older than 5 years presented significantly higher comet length in both olfactory and respiratory epithelia, when compared with controls, indicating DNA damage. When separated by regions, olfactory and respiratory epithelia presented similar DNA damage in dogs from different regions of São Paulo, corroborating with similar levels of particulate matter index (PM10) in all regions of the city. In this study, we report for the first time that the comet assay can be used to quantify the extent of DNA damage in dog olfactory and respiratory epithelia, and that comet length (DNA damage) increases with age, probably due to environmental factors. Air pollution, as measured by PM10, can be responsible for this DNA damage.

Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO2/FiO2 ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity.

Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats.

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO(2)/FiO(2) ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity.

Urban air pollution and chronic obstructive pulmonary disease-related emergency department visits.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can have recurrent disease exacerbations triggered by several factors, including air pollution. Visits to the emergency respiratory department can be a direct result of short-term exposure to air pollution. The aim of this study was to investigate the relationship between the daily number of COPD emergency department visits and the daily environmental air concentrations of PM(10), SO(2), NO(2), CO and O(3) in the City of São Paulo, Brazil. METHODS: The sample data were collected between 2001 and 2003 and are categorised by gender and age. Generalised linear Poisson regression models were adopted to control for both short- and long-term seasonal changes as well as for temperature and relative humidity. The non-linear dependencies were controlled using a natural cubic spline function. Third-degree polynomial distributed lag models were adopted to estimate both lag structures and the cumulative effects of air pollutants. RESULTS: PM(10) and SO(2) readings showed both acute and lagged effects on COPD emergency department visits. Interquartile range increases in their concentration (28.3 microg/m(3) and 7.8 microg/m(3), respectively) were associated with a cumulative 6-day increase of 19% and 16% in COPD admissions, respectively. An effect on women was observed at lag 0, and among the elderly the lag period was noted to be longer. Increases in CO concentration showed impacts in the female and elderly groups. NO(2) and O(3) presented mild effects on the elderly and in women, respectively. CONCLUSION: These results indicate that air pollution affects health in a gender- and age-specific manner and should be considered a relevant risk factor that exacerbates COPD in urban environments.

Tracheal instillation of urban PM(2.5) suspension promotes acute cardiac polarization changes in rats.

The mechanisms by which PM(2.5) increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM(2.5) induces acute cardiac polarization alterations in healthy Wistar rats. PM(2.5) samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 microg PM(2.5) were administered by tracheal instillation. P wave duration decreased significantly at 20 microg (0.99 +/- 0.06, 0.95 +/- 0.06, and 0.96 +/- 0.07; P < 0.001), and 50 microg (0.98 +/- 0.06, 0.98 +/- 0.07, and 0.96 +/- 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 microg (0.99 +/- 0.06, 0.98 +/- 0.07, and 0.97 +/- 0.08) and 50 microg (0.99 +/- 0.05, 0.97 +/- 0.0, and 0.95 +/- 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 microg (P < 0.001). QRS interval duration decreased at 20 and 50 microg in relation to blank filter solution and 10 microg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 microg (0.94 +/- 0.12, 0.88 +/- 0.14, and 0.88 +/- 0.11) and 50 microg (1.00 +/- 0.13; 0.97 +/- 0.11 and 0.98 +/- 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 microg (P < 0.001). PM(2.5) induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.

Tracheal instillation of urban PM2.5 suspension promotes acute cardiac polarization changes in rats

The mechanisms by which PM2.5 increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM2.5 induces acute cardiac polarization alterations in healthy Wistar rats. PM2.5 samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 µg PM2.5 were administered by tracheal instillation. P wave duration decreased significantly at 20 µg (0.99 ± 0.06, 0.95 ± 0.06, and 0.96 ± 0.07; P < 0.001), and 50 µg (0.98 ± 0.06, 0.98 ± 0.07, and 0.96 ± 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 µg (0.99 ± 0.06, 0.98 ± 0.07, and 0.97 ± 0.08) and 50 µg (0.99 ± 0.05, 0.97 ± 0.0, and 0.95 ± 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 µg (P < 0.001). QRS interval duration decreased at 20 and 50 µg in relation to blank filter solution and 10 µg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 µg (0.94 ± 0.12, 0.88 ± 0.14, and 0.88 ± 0.11) and 50 µg (1.00 ± 0.13; 0.97 ± 0.11 and 0.98 ± 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 µg (P < 0.001). PM2.5 induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.